Method and system for determining time-based index for blood circulation from angiographic imaging data

ABSTRACT

A predetermined time-based index ratio such as time-based fractional flow reserve (FFR) is determined for evaluating a level of blood circulation between at least two locations such as a proximal location and a distal location in a selected blood vessel in the region of interest. One time-based FFR is obtained by normalizing a risk artery ratio by a reference artery ratio.

FIELD OF THE INVENTION

The current invention is generally related to an image data processing method and system, and more particularly related to a method or a system for determining a time-based index for blood circulation from imaging data.

BACKGROUND OF THE INVENTION

Relevant prior art has attempted to develop various methods to quantify an extent of blockage of blood circulation. For example, the blockage is often seen as stenosis in a coronary artery, and the extent of blockage is quantified by a predetermined parameter or index. One such widely used index is fractional flow reserve (FFR) for indicating a physiologic significance of coronary artery stenosis.

One area of the prior art attempts has used directly measured pressured data to determine a blockage parameter in a certain blood vessel. By inserting an intracoronary pressure guide wire into a guiding catheter that was introduced to the aorta, the distal coronary pressure and the aortic pressure are measured. After calibration, the pressure guide wire is advanced into coronary artery across stenosis to the most distal artery. As the pressure guide wire tip is kept away from touching the vessel wall, the distal coronary and aortic pressures are recorded simultaneously under maximum coronary vasodilatation. Unfortunately, this measurement technique is an invasive procedure as the pressure wire needs to be inserted into the coronary artery across stenosis and bears some risk.

Another area of the prior art attempts has estimated the FFR from a ratio of a coronary blood flow to a total arterial lumen volume based upon angiographic image data. Unfortunately, in order to quantify the total arterial lumen volume and an associated coefficient, complicated processing procedures are required.

Yet another area of the prior art attempts has utilized angiographic image data in order to study blood circulation. In some attempts, time-density-curves (TDC) or time-intensity-curves (TIC) are constructed for selected regions of interests (ROI) from the angiographic image data. Based upon the TDC or TIC, the blood circulation level is compared among the selected regions. In some of the perfusion imaging techniques, although TDCs are generated from the perfusion images, the TDCs reflect density changes in selected regions or tissues rather than individual blood vessels as ROI. On the other hand, a blood flow speed or a rate of change in blood flow speed is evaluated based upon angiographic image data in individual coronary arteries in one perfusion imaging technique, the blood flow speed is determined based upon a distance traveled along a particular artery by the contrast agent over time. That is, the blood flow speed is deteimined directly from the visual identification of the contrast agent along a blood vessel without the use of time density data such as TDCs.

In view of the above prior art techniques, it remains desirable to implement a clinical index that is useful in evaluating stenosis in a particular blood vessel so as to objectively determine if a certain medical procedure should be performed on a patient.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a diagram illustrating one embodiment of the X-ray cardiovascular apparatus according to the current invention.

FIG. 2 is a diagram illustrating one embodiment of the multi-slice X-ray CT apparatus or scanner according to the current invention.

FIG. 3 is one exemplary image data set with a fixed view angle for optimally visualizing a risk coronary artery to be used for data in the current invention.

FIGS. 4A and 4B illustrate two sets of exemplary images respectively having a different fixed view angle for optimally visualizing a certain coronary artery to be used for data in the current invention.

FIG. 5A is a diagram illustrating exemplary measurement locations for determining density data from the angiographic image data as acquired in a region of interest that includes a predetermined risk artery and a predetermined reference artery according to the current invention.

FIG. 5B is a diagram illustrating exemplary measurement locations for determining density data from the angiographic image data as acquired in a region of interest that includes a predetermined risk artery and a predetermined reference artery that have different shape according to the current invention.

FIG. 5C is a diagram illustrating exemplary measurement locations for determining density data from the angiographic image data as acquired in a region of interest that includes a predetermined risk artery and a predetermined reference artery that share a common location according to the current invention.

FIG. 5D is a diagram illustrating exemplary measurement locations for determining density data from the angiographic image data as acquired in a region of interest that includes a predetermined risk artery and a predetermined reference artery that include regions outside of these arteries according to the current invention.

FIG. 6 is a diagram illustrating a first embodiment of the blood circulation determination device according to the current invention.

FIG. 7 is a pair of exemplary time density curves (TDCs) for illustrating various time indexes to be used in determining the time-based index ratio for evaluating a level of the blood circulation between a proximal location and a distal location in the predeteimined risk blood vessel in the region of interest according to the current invention.

FIG. 8 is a diagram illustrating a second embodiment of the blood circulation determination device according to the current invention.

FIG. 9A illustrates a first pair of exemplary locations for taking intensity measurements on the same branch of a blood vessel such as an artery.

FIG. 9B illustrates a second pair of exemplary locations for taking intensity measurements on the same branch of a blood vessel such as an artery.

FIG. 9C illustrates a third pair of exemplary locations for taking intensity measurements on the same branch of a blood vessel such as an artery.

FIG. 9D illustrates a four pair of exemplary locations for taking intensity measurements on the same branch of a blood vessel such as an artery.

FIG. 9E illustrates a fifth pair of exemplary locations for taking intensity measurements on the same branch of a blood vessel such as an artery.

FIG. 9F illustrates a sixth pair of exemplary locations for taking intensity measurements on different branches of a blood vessel such as an artery.

FIG. 9G illustrates three exemplary locations for taking intensity measurements on the same branch of a blood vessel such as an artery and in a tissue segment near the artery.

FIG. 10A illustrates a user interface where the user specifies the input regions among the displayed options.

FIG. 10B illustrates a user display where the user sees the input region contour that is fused with images.

FIG. 10C illustrates a user display where the user sees numerical values of the new indexes or a map of the new indexes in a region of interest ROI.

FIG. 11 is a flow chart illustrating steps involved in one exemplary process of determining a time-based index ratio for evaluating blood circulation in a predetermined blood vessel or a predetermined tissue segment according to the current invention.

DETAILED DESCRIPTION OF THE EMBODIMENT(S)

Referring now to the drawings, wherein like reference numerals designate corresponding structures throughout the views, and now referring to FIG. 1, a diagram illustrates one embodiment of the X-ray cardiovascular diagnostic apparatus for evaluating blood circulation in a blood vessel according to the current invention. The X-ray diagnostic apparatus includes a high-voltage generator 11, an X-ray tube 12, an X-ray beam limiting device 13, a top plate 14, a C-shaped arm 15, an X-ray detector 16, a C-shaped arm rotating and moving mechanism 17, a top plate moving mechanism 18, a C-shaped-arm and top-plate mechanism controlling unit 19, a beam-limiting controlling unit 20, a system controlling unit 21, an input unit 22, a display unit 23, an image generating unit 24, an image storage unit 25, and an image processing unit 26. In a certain embodiment, a user interface unit 34 includes the input unit 22, the display unit 23 and a certain portion of the system controlling unit 21. Further, as shown in FIG. 1, the X-ray diagnostic apparatus according to the first embodiment is configured so that an electrocardiogram monitor 30 attached to an examined subject P is connected to the image processing unit 26.

In general, X-ray transmission images are generated in the following manner. The X-ray beam limiting device 13 selectively radiates X-ray beams generated by the X-ray tube 12 onto a region of interest including the heart of the subject P. The X-ray detector 16 includes a plurality of X-ray detecting elements for detecting X-ray beams that have passed through the subject P, converting the detected X-ray beams into an electrical signal, storing the electrical signal, and transmitting the stored electrical signal to the image generating unit 24. Thus, an image data acquiring unit includes at least the X-ray detector for acquiring imaging data indicating blood circulation in a region of interest (ROI) including at least in a predetermined risk blood vessel. The image generating unit 24 generates X-ray transmission images based upon the electrical signal and stores the generated X-ray transmission images into the image storage unit 25. The input unit 22 includes one or more of devices such as a touch panel, a touch screen, a mouse, a keyboard, a button, a trackball, and a joystick that are used by an operator like a medical doctor or a technologist who operates the X-ray diagnostic apparatus for the purpose of inputting various types of commands. One of the commands is to specify a region of interest using a particular user interface unit in the input unit 22. The input unit 22 transfers the commands that have been received from the operator to the system controlling unit 21.

In further detail, the user interface unit 34 in one embodiment includes the display unit 23 and the input unit 22 for providing certain features according to the current invention. Using the user interface unit 34 such as a Graphical User Interface (GUI), the operator manually specifies a ROI in the displayed image for evaluating blood circulation in a blood vessel or a tissue region according to the current invention. The display unit 23 indicates a contour of an input region or a ROI that has been specified for evaluating blood circulation in a manner that is fused with the displayed image. In one embodiment, the display unit also displays the blood circulation evaluation results either in numerical values of a predetermined time-based index and or in a predetermined graphical form. In one predetermined graphical form, the time-based index value is plotted in the Y axis while the selected regions (ROIs) are plotted in the X axis as illustrated in FIG. 10A. In another predetermined graphical form, the time-based index value is plotted in the Y axis while the selected points along a predetermined line in a ROI are plotted in the X axis as illustrated in FIG. 10B. In yet another predetermined graphical form, the time-based index values are mapped in the X-Y coordinate with respect to a selected structure such as a blood vessel as illustrated in FIG. 10C.

Still referring to FIG. 1, the above embodiment of the X-ray cardiovascular diagnostic apparatus evaluates blood circulation in a blood vessel according to the current invention. The electrocardiogram monitor 30 obtains an electrocardiogram (ECG) waveform of the subject P and transmits the obtained electrocardiogram waveform together with time and movement information to the image processing unit 26. The image processing unit connected to the image data acquiring unit for performing various processing such as ECG gating, motion compensation and background subtraction on the imaging data. A time density generating unit 32 is connected to the image processing unit 26 for generating time density data in the ROI from the imaging data at a proximal location and a distal location at least with respect to the predetermined risk blood vessel. In general, the proximal location is proximal to a suspected stenosis in the predetermined risk blood vessel while the distal location is distal to the suspected stenosis. Furthermore, a time-based index determining unit 33 is connected to the time density generating unit 32 for determining based upon the time density data a time-based index for evaluating a level of the blood circulation between the proximal location and the distal location in the ROI.

The C-shaped arm 15 supports the X-ray tube 12, the X-ray beam limiting device 13, and the X-ray detector 16 while the C-shaped arm rotating and moving mechanism 17 rotates and moves the C-shaped arm 15 under the control of the C-shaped-arm and top-plate mechanism controlling unit 19.

In summary, the X-ray diagnostic apparatus according to the first embodiment generates X-ray transmission images by radiating the X-ray beams onto the heart of the subject P in which a contrast agent has been injected into the coronary arteries. Further, the X-ray diagnostic apparatus according to the first embodiment determines blood circulation levels in regions of interest such as a blood vessel or tissue regions based upon a predetermined time-base index such as fractional flow reserve (FFR) according to the current invention.

Now referring to FIG. 2, a diagram illustrates one X-ray CT apparatus or scanner according to the current invention including a gantry 100 and other devices or units. The gantry 100 is illustrated from a side view and further includes an X-ray tube 101, an annular frame 102 and a multi-row or two-dimensional array type X-ray detector 103. The X-ray tube 101 and X-ray detector 103 are diametrically mounted across a subject S on the annular frame 102, which is rotatably supported around a rotation axis RA. A rotating unit 107 rotates the frame 102 at a high speed such as 0.4 sec/rotation while the subject S is being moved along the axis RA into or out of the illustrated page.

The multi-slice X-ray CT apparatus further includes a high voltage generator 109 and a current regulator 111 that respectively control a tube voltage and a tube current in the X-ray tube 101 through a slip ring 108 so that the X-ray tube 101 generates X ray in response to a system controller 110. The X rays are emitted towards the subject S, whose cross sectional area is represented by a circle. The X-ray detector 103 is located at an opposite side from the X-ray tube 101 across the subject S for detecting the emitted X rays that have transmitted through the subject S. The X-ray detector 103 further includes individual detector elements or units that are conventional integrating detectors.

Still referring to FIG. 2, the X-ray CT apparatus or scanner further includes other devices for processing the detected signals from X-ray detector 103. A data acquisition circuit or a Data Acquisition System (DAS) 104 converts a signal output from the X-ray detector 103 for each channel into a voltage signal, amplifies it, and further converts it into a digital signal. The X-ray detector 103 and the DAS 104 are configured to handle a predetermined total number of projections per rotation (TPPR) that can be at the most 900 TPPR, between 900 TPPR and 1800 TPPR and between 900 TPPR and 3600 TPPR.

The above described data is sent to a preprocessing device 106, which is housed in a console outside the gantry 100 through a non-contact data transmitter 105. The preprocessing device 106 performs certain corrections such as sensitivity correction on the raw data. A storage device 112 then stores the resultant data that is also called projection data at a stage immediately before reconstruction processing. The storage device 112 is connected to the system controller 110 through a data/control bus, together with a reconstruction device 114, an input device 115, a display device 116, a blood circulation determination device 117, a treatment deteiuiination device 118 and the scan plan support apparatus 200. The scan plan support apparatus 200 includes a function for supporting an imaging technician to develop a scan plan.

In one embodiment of the current invention, a perfusion-related equipment is required to perform the injection of a predetermined contrast agent into the subject S. For example, a predetermined contrast agent is injected in bolus into the left ventricular cavity in a coronary study prior to scanning. The details of a perfusion technique is not going to be described in details here, but well-known perfusion techniques are generally applicable to the current invention.

One embodiment of the blood circulation determination device 117 further includes a combination of various software and hardware components. According to one aspect of the current invention, the blood circulation determination device 117 of the CT apparatus advantageously determines a predetermined time-based fractional flow reserve (FFR) based upon the angiographic image data that is acquired by the X-ray CT apparatus. In general, the blood circulation determination device 117 in one embodiment of the current invention initially generates time density data such as time-density curves (TDCs) at predetermined locations along a selected blood vessel from the angiographic image data. The predetermined locations generally include at least a proximal location and a distal location. The proximal location is proximal to a suspected stenosis location in the selected blood vessel and is substantially free from any blockage for blood circulation. On the other hand, the distal location is distal to the suspected stenosis location in the selected blood vessel and is potentially affected by the blockage for blood circulation. Ultimately, the blood circulation determination device 117 determines a predetermined time-based index such as time-based FFR for evaluating a level of blood circulation between two locations such as the proximal location and the distal location in a selected blood vessel in the region of interest. Thus, a total of two data points is used to determine a time-based FFR in the first embodiment of the blood circulation determination device 117 according to the current invention.

In a second embodiment of the blood circulation determination device 117 also further includes a combination of various software and hardware components. According to one aspect of the current invention, the blood circulation determination device 117 of the CT apparatus advantageously determines a predetermined time-based fractional flow reserve (FFR) based upon the angiographic image data that is acquired by the X-ray CT apparatus. In general, the blood circulation determination device 117 in a second embodiment of the current invention initially generates time density data such as time-density curves (TDCs) at predetermined locations along a pair of selected blood vessels from the angiographic image data. The pair of selected blood vessels generally includes a predetermined risk blood vessel and a predetermined reference blood vessel. The predetermined risk blood vessel is a blood vessel under investigation for a suspected stenosis that contributes to some blockage in blood circulation. On the other hand, the predetermined reference blood vessel is a separate blood vessel from the predetermined risk blood vessel and is used as a reference to assure the evaluation for a suspected stenosis in the predetermined risk blood vessel. In general, the predetermined reference blood vessel is selected from a group of healthy blood vessels that is comparable in size and location to the predetermined risk blood vessel and is substantially from stenosis.

In the second embodiment of the current invention, the blood circulation determination device 117 also generates time density data such as time-density curves (TDCs) at the predetermined locations along each of the selected pair of the blood vessels from the angiographic image data. The predetermined locations generally include at least a proximal location and a distal location along each of the two selected blood vessels. In the predetermined risk blood vessel, the proximal location is proximal to a suspected stenosis location and is substantially free from any blockage for blood circulation. On the other hand, the distal location in the predetermined risk blood vessel is distal to the suspected stenosis location and is potentially affected by the blockage for blood circulation. In the predetermined reference blood vessel, the proximal and distal locations are each a location that is respectively comparable to the proximal location and the distal location of the predetermined risk blood vessel. Ultimately, the blood circulation determination device 117 determines a predetermined time-based index such as time-based FFR for evaluating a level of blood circulation between two locations such as the proximal location and the distal location in a selected blood vessel in the region of interest. Thus, a total of four data points is used to determine a time-based FFR in the second embodiment of the blood circulation determination device 117 according to the current invention.

One embodiment of the treatment determination device 118 further includes various software and hardware components. According to one aspect of the current invention, the treatment determination device 118 of the CT apparatus advantageously determines as to whether or not a certain medical procedure should be performed on the patient based upon the blockage index that the blood circulation determination device 117 has outputted for a particular blood vessel. For example, if the blood circulation determination device 117 outputted a particular FFR value, the treatment determination device 118 advantageously determines as to whether or not a stent should be inserted into the measured coronary artery based upon the FFR value and outputs a proposed medical decision. The treatment determination device 118 optionally displays the relevant information including the proposed medical decision via the display device 116.

As will be further described below, the current invention is not limited to the specific features of the above disclosures. The blood circulation determination device 117 according to the current invention is not limited certain aspects of the time density data to determine a predetermined fractional flow reserve (FFR). For example, one embodiment of the blood circulation determination device 117 utilizes the time-to-peak (TTP) information, mean-transit-time (MTT) information and or upward slope information of the time-density curves (TDC), another embodiment optionally uses different aspects of the time density data that has been generated from the angiographic image data with respect to the blood vessels and the surrounding tissues. By the same token, the treatment determination device 118 optionally considers other factors or information in addition to the output index from the blood circulation determination device 117.

By the same token, the current invention is not limited to the specific features of the above disclosed embodiments of the CT apparatus. In other words, the current invention is applicable to other modalities including ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), angiography and positron emission tomography (PET). In fact, one embodiment of the current invention is implemented on a C-arm X-ray system in angiography. In this regard, the time density data such as time-density curves (TDCs) is generated from certain imaging data including but not limited to angiographic image data and angiographic imaging data.

Now referring to FIG. 3, one exemplary image data set has a fixed view angle for optimally visualizing a risk coronary artery according to the current invention. The exemplary X-ray image is a 2-dimensional image. Because of an optimal projection view-angle, one data acquisition protocol is to measure all the data points from the same single image set. The exemplary X-ray image shows on the left hand side a predetermined risk blood vessel and a predetermined risk region of interest (ROI). Similarly, the same exemplary X-ray image shows on the right hand side the predetermined reference blood vessel and a predetermined reference region of interest (ROI) that are comparable in size and location to the predetermined risk blood vessel and the predetermined risk region of interest (ROI) as shown in the left hand side. A plurality of density measurements is taken from the single image, and other density measurements are also made from comparable single images that have been scanned at the optimal projection view-angle over time. Based upon the these measurements, time density data is generated as risk time density curves (TDCs) and reference time density curves (TDCs) from one set of images according to a first data acquisition protocol of the current invention.

Now referring to FIGS. 4A and 4B, two sets of exemplary images respectively have a different fixed view angle for optimally visualizing a certain coronary artery according to the current invention. The exemplary X-ray images are each a 2-dimensional image, and the two image data sets each have an optimal view-angle. That is, the data sets of FIGS. 4A and 4B respectively have a different optimal projection view-angle to a risk coronary artery and a reference coronary artery. Because of a different optimal projection view-angle, a second data acquisition protocol is to measure some data points from one image set and other data points from the other image set. The exemplary X-ray image as illustrated in FIG. 4A shows on the left hand side a predetermined risk blood vessel and a predetermined risk region of interest (ROI).

Similarly, the exemplary X-ray image as illustrated in FIG. 4B shows also on the left hand side the predetermined reference blood vessel and a predetermined reference region of interest (ROI) that are comparable in size and location to the predetermined risk blood vessel and the predetermined risk region of interest (ROI) as shown in the left hand side of FIG. 4A. A plurality of density measurements is taken from the two image sets, and other density measurements are also made from comparable image data sets that have been scanned at the different optimal projection view-angles over time. Based upon the these measurements, time density data is generated as risk time density curves (TDCs) and reference time density curves (TDCs) from two sets of images according to a second data acquisition protocol of the current invention.

Now referring to FIG. 5A, a diagram illustrates exemplary measurement locations for determining density data from the angiographic image data as acquired in a region of interest that includes a predetermined risk artery and a predetermined reference artery according to the current invention. In this and other examples, the term, artery is synonymously used with a blood vessel, and blood vessels generally include arteries and veins as well as capillaries. On the left side, a predetermined risk artery Rsk is shown with a stenosis ST that restricts blood flow due to its blocking effect. Across the stenosis ST, a risk artery proximal location PRsk is located closer to a artery branching point Br where blood flows towards the risk artery proximal location PRsk along the predetermined risk artery Rsk. On the other hand, a risk artery distal location DRsk is located further away from the artery branching point Br across the stenosis ST along the predetermined risk artery Rsk.

Still referring to FIG. 5A, on the right side, a predetermined reference artery Ref is shown to be substantially free from any stenosis and to be comparable in size and location to the predetermined risk artery Rsk. Since the thickness of the two arteries Ref and Rsk are substantially equal over the equal distance L₁ and L₂, the predetermined reference artery Ref is comparable to the predetermined risk artery Rsk in size. Furthermore, because of the symmetrical configuration across the artery branching point Br, the predetermined reference artery Ref is also comparable to the predetermined risk artery Rsk in location. In this regard, a reference artery proximal location PRef is located along the predetermined reference artery Ref and as comparably close to the artery branching point Br as the risk artery proximal location PRsk. On the other hand, a reference artery distal location DRef is located along the predetermined reference artery Ref and comparably further away from the artery branching point Br as the risk artery distal location DRsk. In this embodiment, a total of four data points is determined at the risk artery proximal location PRsk, the risk artery distal location DRsk, the reference artery proximal location PRef and the reference artery distal location DRef for generating density data according to the current invention.

Now referring to FIG. 5B, a diagram illustrates exemplary measurement locations for determining density data from the angiographic image data as acquired in a region of interest that includes a predetermined risk artery and a predetermined reference artery according to the current invention. On the left side, a predetermined risk artery Rsk is shown with a stenosis ST that restricts blood flow due to its blocking effect. Across the stenosis ST, a risk artery proximal location PRsk is located closer to a artery branching point Br where blood flows towards the risk artery proximal location PRsk along the predetermined risk artery Rsk. On the other hand, a risk artery distal location DRsk is located further away from the artery branching point Br across the stenosis ST along the predetermined risk artery Rsk.

Still referring to FIG. 5B, on the right side, a predetermined reference artery Ref is shown to be substantially free from any stenosis and to be comparable in size and location to the predetermined risk artery Rsk. Since the thickness of the two arteries Ref and Rsk are substantially equal over the equal distance L₁ and L₂, the predetermined reference artery Ref is comparable to the predetermined risk artery Rsk in size. Despite the asymmetrical configuration across the artery branching point Br, the predetermined reference artery Ref is still assumed to be comparable to the predetermined risk artery Rsk in location due to their vicinity with each other and common branching point Br. In this regard, a reference artery proximal location PRef is located along the predetermined reference artery Ref and as comparably close to the artery branching point Br as the risk artery proximal location PRsk. On the other hand, a reference artery distal location DRef is located along the predetermined reference artery Ref and comparably further away from the artery branching point Br as the risk artery distal location DRsk. In this embodiment, a total of four data points is determined at the risk artery proximal location PRsk, the risk artery distal location DRsk, the reference artery proximal location PRef and the reference artery distal location DRef for generating density data according to the current invention.

Now referring to FIG. 5C, a diagram illustrates exemplary measurement locations for determining density data from the angiographic image data as acquired in a region of interest that includes a predetermined risk artery and a predetermined reference artery according to the current invention. On the left side, a predetermined risk artery Rsk is shown with a stenosis ST that restricts blood flow due to its blocking effect. Across the stenosis ST, a common proximal location P is located upstream and near an artery branching point Br where the predetermined risk artery Rsk and the predetermined reference artery Ref branch. On the other hand, a risk artery distal location DRsk is located further away from the artery branching point Br across the stenosis ST along the predetermined risk artery Rsk.

Still referring to FIG. 5C, on the right side, the predetermined reference artery Ref is shown to be substantially free from any stenosis and to be comparable in size and location to the predetermined risk artery Rsk. Since the thickness of the two arteries Ref and Rsk are substantially equal over the equal distance L₁ and L₂, the predetermined reference artery Ref is comparable to the predetermined risk artery Rsk in size. Because of the substantially symmetrical configuration across the artery branching point Br, the predetermined reference artery Ref is assumed to be comparable to the predetermined risk artery Rsk in location due to their vicinity with each other and the common branching point Br. In this regard, the common proximal location is shared between the predetermined reference artery Ref and the predetermined risk artery Rsk. On the other hand, a reference artery distal location DRef is located along the predetermined reference artery Ref and comparably further away from the artery branching point Br as the risk artery distal location DRsk. In this embodiment, a total of three data points is determined at the common proximal location P, the risk artery distal location DRsk, and the reference artery distal location DRef for generating density data according to the current invention.

Now referring to FIG. 5D, a diagram illustrates exemplary measurement locations for determining density data from the angiographic image data as acquired in a region of interest that includes a predetermined risk artery and a predetermined reference artery according to the current invention. In this and other examples, the term, artery is synonymously used with a blood vessel, and blood vessels generally include arteries and veins as well as capillaries. On the left side, a predetermined risk artery Rsk is shown with a stenosis ST that restricts blood flow due to its blocking effect. Across the stenosis ST, a risk artery proximal location PRsk is located closer to an artery branching point Br where blood flows towards the risk artery proximal location PRsk along the predetermined risk artery Rsk. On the other hand, a risk artery distal region DRsk is located further away from the artery branching point Br across the stenosis ST along the predetermined risk artery Rsk.

Still referring to FIG. 5D, on the right side, a predetermined reference artery Ref is shown to be substantially free from any stenosis and to be comparable in size and location to the predetermined risk artery Rsk. Since the thickness of the two arteries Ref and Rsk are substantially equal over the equal distance L₁ and L₂, the predetermined reference artery Ref is comparable to the predetermined risk artery Rsk in size. Furthermore, because of the symmetrical configuration across the artery branching point Br, the predetermined reference artery Ref is also comparable to the predetermined risk artery Rsk in location. In this regard, a reference artery proximal location PRef is located inside and along the predetermined reference artery Ref and as comparably close to the artery branching point Br as the risk artery proximal location PRsk located inside and along the predetermined risk artery Rsk. On the other hand, a reference artery distal location DRef is a region located outside the predetermined reference artery Ref and comparably further away from the artery branching point Br as the risk artery distal location DRsk also a region located outside the predetermined risk artery Rsk. In this embodiment, a total of four data points is determined at the risk artery proximal location PRsk, the risk artery distal region DRsk, the reference artery proximal location PRef and the reference artery distal region DRef for generating density data according to the current invention.

Now referring to FIG. 6, a diagram illustrates one embodiment of the blood circulation determination device 117 according to the current invention. In general, one embodiment of the blood circulation determination device 117A advantageously determines a predetermined time-based fractional flow reserve (FFR) based upon the angiographic image data that is acquired by a myocardial perfusion imaging apparatus. The blood circulation determination device 117A further includes a perfusion image data initial processing unit 1000, a time-density curves (TDC) generation unit 1100, a TDC index generation unit 1200 and a time-based fractional flow reserve (FFR) generation outputting unit 1300. The following description is illustrated that one embodiment of the blood circulation determination device 117A determines a FFR based upon the angiographic image data of coronary arteries and supported myocardium.

In general, a data set of myocardial perfusion images is a time sequence of images of heart blood flow from the entrance of a coronary artery into myocardium. The image data include images before contrast agent injection and, of contrast agent inflow and outflow. All the measurement images are selected at a substantially identical cardiac phase with retrospective cardiac gating. A change in image intensity in contrast agent pixels represents heart blood flow. Time density curve measurements of blood flow are implemented on background subtraction images with motion compensation.

The perfusion image data initial processing unit 1000 extracts a first region of interest (ROI) 1000A including a risk coronary artery and supported myocardium 1 as well as a second region of interest (ROI) 1000B including a healthy or reference coronary artery and supported myocardium 2. The perfusion image data initial processing unit 1000 outputs the extracted image data of the first region of interest (ROI) 1000A and the second region of interest (ROI) 1000B to the time-density curves (TDC) generation unit 1100. The pair of selected arteries generally includes a predetermined risk artery and a predetermined reference artery. The predetermined risk artery is a blood vessel under investigation for a suspected stenosis that contributes to some blockage in blood circulation. On the other hand, the predetermined reference artery is a separate blood vessel from the predetermined risk artery and is used as a reference to assure the evaluation for a suspected stenosis in the predetermined risk artery. In general, the predetermined reference artery is selected from a group of healthy blood vessels that is comparable in size and location to the predetermined risk artery and is substantially from stenosis.

The time-density curves (TDC) generation unit 1100 generates four time-density curves. That is, the time-density curves (TDC) generation unit 1100 generates a first pair of a proximal artery TDC 1A and a corresponding myocardial TDC 1B for the risk coronary artery based upon the first region of interest (ROI) 1000A. By the same token, the time-density curves (TDC) generation unit 1100 also generates a second pair of a proximal artery TDC 2A and a corresponding myocardial TDC 2B for the reference coronary artery based upon the second region of interest (ROI) 1000A. The proximal artery TDC 1A is a time-density curve that is generated based upon the density data at a proximal artery location where is upstream with respect to a suspected stenosis along the risk coronary artery. The corresponding myocardial TDC 1B is a time-density curve that is generated based upon the density data at a corresponding distal location where is downstream with respect to the proximal artery location along the risk coronary artery. T Similarly, the proximal artery TDC 2A is a time-density curve that is generated based upon the density data of the reference artery at a proximal artery location where is comparable to the risk proximal artery location. The corresponding myocardial TDC 2B is a time-density curve that is generated based upon the density data at a corresponding distal location where is downstream with respect to the proximal artery location along the reference coronary artery. The time-density curves (TDC) generation unit 1100 further includes a TDC fitting unit 1100A to further process the above four TDCs 1A, 1B, 2A and 2B with a predetermined fitting model such as gamma-variate model.

The TDC index generation unit 1200 generally calculates a risk ratio based upon selected time indexes. The TDC index generation unit 1200 further includes a time index ratio calculation unit 1200A for selecting a time index of each of the fitted TDCs 1A, 1B, 2A and 2B and for determining a time index ratio based upon the selected time indexes. That is, the TDC index generation unit 1200 selects an time index of a TDC such as a time-to-peak (TTP) index or a mean-transit-time (MMT) index and determines a time value for the selected time index from each of the fitted TDCs 1A, 1B, 2A and 2B. Subsequently, the time index ratio calculation unit 1200A calculates a time index ratio of the risk coronary artery TIRA based upon the selected index pair in the TDCs 1A and 1B. Similarly, the time index ratio calculation unit 1200A also calculates a time index ratio of the reference coronary artery TIRB based upon the selected index pair in the TDCs 2A and 2B.

Still referring to FIG. 6, the time-based fractional flow reserve (FFR) generation outputting unit 1300 further includes an index ratio normalization unit 1300A for normalizing the risk ratio TIRA by the reference ratio TIRB to determine a time-based fractional flow reserve (FFR) index. Ultimately, the blood circulation determination device 117A determines the time-based FFR for evaluating a level of blood circulation between two locations such as the proximal location and the distal location in a selected coronary risk artery with respect to the comparable locations in the selected coronary reference artery. Thus, a total of four TDCs 1A, 1B, 2A and 2B is used to determine a time-based FFR in the embodiment of the blood circulation determination device 117A according to the current invention.

In the above exemplary embodiment, myocardial perfusion images are used to illustrate a process in which the time-based FFR is determined. This exemplary process and embodiment are mere illustration, and the current invention is not limited to the use of myocardial angiographic image data or the determination of the time-based FFR for the coronary arteries. The current invention is applicable to evaluate blood circulation in blood vessels in various organs.

Now referring to FIG. 7, a pair of exemplary time density curves (TDCs) is provided for illustrating various time indexes to be used in determining the time-based index ratio for evaluating a level of the blood circulation between a proximal location and a distal location in the predetermined risk blood vessel in the region of interest according to the current invention. The two exemplary TDCs are plotted with the X axis indicating time and the Y axis indicating intensity of a pixel or a group of pixels in a predetermined region of interest (ROI). One of the two exemplary TDCs is a proximal artery TDC based upon intensity measurements at a predetermined proximal location along a predetermined artery as illustrated in the dotted line. The other of the two exemplary TDCs is a distal artery TDC or myocardial TDC based upon intensity measurements at a predetermined distal or myocardial location along the predetermined artery as illustrated in the solid line.

Still referring to FIG. 7, certain time indexes are described with respect to the two exemplary TDCs according to the current invention. A first exemplary time index is a time-to-peak (TTP). With respect to the proximal artery TDC, its TTP is denoted by TTP_(p), which indicates an amount of time to reach a peak point in the proximal artery TDC. Similarly, with respect to the distal artery TDC, its TTP is denoted by TTP_(m), which indicates an amount of time to reach a peak point in the distal artery TDC. Thus, one exemplary time index ratio for a predetermined risk artery is TTP_(p)/TTP_(m). A second exemplary time index is a fractional time-to-peak (xTTP), where x is a predetermined percentage. With respect to the proximal artery TDC, its xTTP is denoted by xTTP_(p), which indicates an amount of time to reach a predetermined percentage of the peak point in the proximal artery TDC. Similarly, with respect to the distal artery TDC, its xTTP is denoted by xTTP_(m), which indicates an amount of time to reach a predetermined percentage of the peak point in the distal artery TDC. Thus, one exemplary time index ratio is xTTP_(p)/xTTP_(m). A third exemplary time index is a mean-transit-time (MTT). Alternatively, an upward slope of the fitted TDC is optionally used as the time index in another embodiment.

With respect to FIG. 7, only one pair of TDCs is illustrated for the sake of simplicity. As discussed above with respect to FIG. 6, a total of four TDCs 1A, 1B, 2A and 2B is used to determine a time-based FFR in the embodiment of the blood circulation determination device 117A according to the current invention. In this regard, a second pair of TDCs is optionally plotted in the same graph for a predetermined reference artery. Using the above described first exemplary time index TTP, with respect to the proximal reference artery TDC, its TTP is denoted by TTP_(ref) _(—) _(p), which indicates an amount of time to reach a peak point in the proximal reference artery TDC. Similarly, with respect to the distal reference artery TDC, its TTP is denoted by TTP_(ref) _(—) _(m), which indicates an amount of time to reach a peak point in the distal reference artery TDC. Thus, for the predetermined reference artery, one exemplary time index ratio is TTP_(ref) _(—) _(p)/TTP_(ref) _(—) _(m). The above discussed exemplary time index ratio for a predetermined risk artery is TTP_(p)/TTP_(m) is thus normalized by the predetermined reference artery time index ratio, TTP_(ref) _(—) _(p)/TTP_(ref) _(—) _(m) to obtain a time-based fractional flow reserve (FFR) as follows in Equation (1):

$\begin{matrix} {{FFR} = {\frac{{TTP}_{p}}{{TTP}_{m}} \times \frac{{TTP}_{ref\_ m}}{{TTP}_{ref\_ p}}}} & (1) \end{matrix}$

To account for some perfusion characteristics, the following Equation (2) includes additional term.

$\begin{matrix} {{FFR} = {\frac{{TTP}_{p}}{{TTP}_{m}} \times \frac{{TTP}_{ref\_ m}}{{TTP}_{ref\_ p}} \times \frac{E_{ref\_ m}}{E_{m}}}} & (2) \end{matrix}$

where

$\begin{matrix} \frac{E_{ref\_ m}}{E_{m}} & \; \end{matrix}$

is a ration of extraction fractions of myocardium for the reference artery and the risk artery.

The FFR of Equation (2) is optionally modified based upon xTTP as defined in the following Equation (3):

$\begin{matrix} {{FFR} = {\frac{{xTTP}_{p}}{{xTTP}_{m}} \times \frac{{xTTP}_{ref\_ m}}{{xTTP}_{ref\_ p}} \times \frac{E_{ref\_ m}}{E_{m}}}} & (3) \end{matrix}$

The FFR is optionally determined based upon MMT as defined in the following Equation (4):

$\begin{matrix} {{FFR} = {\frac{{MTT}_{p}}{{MTT}_{m}} \times \frac{{MTT}_{ref\_ m}}{{MTT}_{ref\_ p}} \times \frac{E_{ref\_ m}}{E_{m}}}} & (4) \end{matrix}$

The FFR is alternatively determined based upon slopes as defined in the following Equation (5):

$\begin{matrix} {{FFR} = {\frac{{Slope}_{p}}{{Slope}_{m}} \times \frac{{Slope}_{ref\_ m}}{{Slope}_{ref\_ p}} \times \frac{E_{ref\_ m}}{E_{m}}}} & (5) \end{matrix}$

The above definition of the fractional flow reserve (FFR) is a ratio that is based upon the assumed relation between a risk artery and a healthy reference artery in a ratio of the blood volume and a ratio of the blood flow time as obtained from the time density data. The following equation (6) provides the relation:

$\begin{matrix} {\frac{V_{s}}{V_{p}} = {\frac{V_{ref\_ d}}{V_{ref\_ p}} = \frac{T_{ref\_ d}}{T_{ref\_ p}}}} & (6) \end{matrix}$

where V_(S) is a blood volume parameter at a risk artery having stenosis while V_(P) is a blood volume parameter at a proximal location to the stenosis in the risk artery. V_(ref) _(—) _(d) is a blood volume parameter at a distal location in a healthy or reference artery while V_(ref) _(—) _(d), is a blood volume parameter at a proximal location in the healthy or reference artery. T_(ref) _(—) _(d) is a time parameter in the time density data at a distal location in the healthy or reference artery while T_(ref) _(—) _(p) is a time parameter in the time density data at a proximal location in the healthy or reference artery. The reference proximal and distal locations correspond to those in the risk artery having stenosis.

Now referring to FIG. 8, a diagram illustrates a second embodiment of the blood circulation determination device 117 according to the current invention. In general, one embodiment of the blood circulation determination device 117B advantageously determines a predetermined time-based fractional flow reserve (FFR) based upon the angiographic image data that is acquired by a myocardial perfusion imaging apparatus. The blood circulation determination device 117B further includes a perfusion image data initial processing unit 1001, a time-density curves (TDC) generation unit 1101, a TDC index generation unit 1201 and a time-based fractional flow reserve (FFR) generation outputting unit 1301. The following description is illustrated that one embodiment of the blood circulation determination device 117B determines a FFR based upon the angiographic image data of coronary arteries and supported myocardium.

In general, a data set of myocardial perfusion images is a time sequence of images of heart blood flow from the entrance of a coronary artery into myocardium. The image data include images before contrast agent injection and, of contrast agent inflow and outflow. All the measurement images are selected at a substantially identical cardiac phase with retrospective cardiac gating. A change in image intensity in contrast agent pixels represents heart blood flow. Time density curve measurements of blood flow are implemented on background subtraction images with motion compensation.

The perfusion image data initial processing unit 1001 extracts a region of interest (ROI) 1001A including a risk coronary artery and supported myocardium. The perfusion image data initial processing unit 1001 outputs the extracted image data of the region of interest (ROI) 1001A to the time-density curves (TDC) generation unit 1101. The predetermined risk artery is a blood vessel under investigation for a suspected stenosis that contributes to some blockage in blood circulation.

The time-density curves (TDC) generation unit 1101 generates two time-density curves. That is, the time-density curves (TDC) generation unit 1101 generates a pair of a proximal artery TDC 1A and a corresponding myocardial TDC 1B for the predetermined risk coronary artery based upon the region of interest (ROI) 1001A. The proximal artery TDC 1A is a time-density curve that is generated based upon the density data at a proximal artery location where is upstream with respect to a suspected stenosis along the risk coronary artery. The corresponding myocardial TDC 1B is a time-density curve that is generated based upon the density data at a corresponding distal location where is downstream with respect to the proximal artery location along the risk coronary artery. The time-density curves (TDC) generation unit 1101 further includes a TDC fitting unit 1101A to further process the above four TDCs 1A and 1B with a predetermined fitting model such as gamma-variate model.

The TDC index generation unit 1201 generally calculates a ratio based upon selected time indexes. The TDC index generation unit 1201 further includes a time index ratio calculation unit 1201A for selecting a time index of each of the fitted TDCs 1A and 1B, and for determining a time index ratio based upon the selected time indexes. That is, the TDC index generation unit 1201 selects an time index of a TDC such as a time-to-peak (TTP) index or a mean-transit-time (MMT) index and determines a time value for the selected time index from each of the fitted TDCs 1A and 1B. Subsequently, the time index ratio calculation unit 1201A calculates a time index ratio of the risk coronary artery TIRA based upon the selected index pair in the TDCs 1A and 1B.

Still referring to FIG. 8, the time-based fractional flow reserve (FFR) generation outputting unit 1301 further includes an index ratio normalization unit 1301A for optionally normalizing the risk ratio TIRA by a predetermined value to determine a time-based fractional flow reserve (FFR) index. Ultimately, the blood circulation determination device 117B determines the time-based FFR for evaluating a level of blood circulation between two locations such as the proximal location and the distal location in a selected coronary risk artery. Thus, a total of two TDCs 1A and 1B is used to determine a time-based FFR in the embodiment of the blood circulation determination device 117B according to the current invention.

Now referring to FIGS. 9A through 9G, diagrams illustrate particular examples of the locations where intensity measurements are taken in order to generate time density curves according to the current invention. FIG. 9A illustrates two exemplary locations for taking intensity measurements on the same branch of a blood vessel such as an artery. The two locations on the same branch of the arteries include a proximal location P1 and a distal location D1, and the two locations have a predetermined distance between them along the blood vessel. The time density curves are generated based upon the time density data measures at the two locations.

FIG. 9B illustrates exemplary locations for taking intensity measurements on the same branch of a blood vessel such as an artery. The locations on the same branch of the arteries include a proximal location P2 and a predetermined number of distal locations D2 ₁ through D2 _(n), and all of these locations are located inside and along the artery. In one technique, the measurements at the predetermined number of distal locations D2 ₁ through D2 _(n) are collectively used as a second location. The time density curves are generated based upon the time density data measures at these two locations.

FIG. 9C illustrates exemplary locations for taking intensity measurements on the same branch of a blood vessel such as an artery. The locations on the same branch of the arteries include a proximal location P3 and a predetermined number of distal locations D3 along a central line of the artery as illustrated in a dotted line, and all of these locations are located inside and along the artery. In one technique, the measurements at the predetermined number of distal locations D3 are collectively used as a second location. The time density curves are generated based upon the time density data measures at these two locations.

FIG. 9D illustrates exemplary locations for taking intensity measurements on the same branch of a blood vessel such as an artery. The locations on the same branch of the arteries include a proximal location P4 and a predetermined number of distal locations D4 ₁ through D4 _(n), and all of these locations are located at image pixels outside the artery. In one technique, the measurements at the predetermined number of distal locations D4 ₁ through D4 _(n) are collectively used as a second location. The time density curves are generated based upon the time density data measures at these two locations.

FIG. 9E illustrates exemplary locations for taking intensity measurements on the same branch of a blood vessel such as an artery. The locations on the same branch of the arteries include a proximal location P5 and a predetermined distal tissue area or segment D5 near the artery as illustrated by an enclosed area, and all of these locations are located outside the artery. In one technique, the measurements in the predetermined distal tissue area D5 are collectively used as a second location. The time density curves are generated based upon the time density data measures at these two locations.

FIG. 9F illustrates two exemplary locations for taking intensity measurements on different branches of a blood vessel such as an artery. The two locations on the two branches of the arteries include a first location P6 and a second location D6, and the two locations have an approximately same distance from the branching point along the blood vessel. In this example, a stenosis is illustrated upstream of the first location P6. The time density curves are generated based upon the time density data measures at the two locations.

FIG. 9G illustrates three exemplary locations for taking intensity measurements on the same branch of a blood vessel such as an artery and in a tissue segment near the artery. The two locations on the same branch of the arteries include a first location P7 and a second location D7 ₁, and a tissue segment D7 ₂ is located outside the artery near the second location D7 ₁. In this example, a stenosis is illustrated upstream of the second location D7 ₁. The time density curves are generated based upon the time density data measures at the three locations. Thus, a time-based index ratio is ultimately determined from a combination of the three TDCs. For example, the time-based index ratio is determined between the time at the proximal vessel location P7 and the distal vessel location D7 ₁. A second example of the time-based index ratio is determined between the distal vessel location D7 ₁ and the distal segment tissue D7 ₂. A third example of the time-based index ratio is determined between the proximal vessel location P7 and the distal segment tissue D7 ₂.

Now referring to FIGS. 10A through 10C, diagrams illustrate exemplary displays or user interface for the time-based fractional flow reserve (FFR) values as determined by the embodiments of the current invention. FIG. 10A illustrates a user interface where the user specifies the input regions among the displayed options 1 through 4. FIG. 10B illustrates a user display where the user sees the input region contour that is fused with images. FIG. 10C illustrates a user display where the user sees numerical values of the new indexes or a map of the new indexes in a region of interest ROI. The above graphical presentations of the FFR values are merely exemplary, and the embodiments of the current invention are not limited to the above examples. For example, the embodiments of the current invention optionally display the FFR values in a predetermined table format.

Now referring to FIG. 11, a flow chart illustrates steps involved in one exemplary process of determining a time-based index ratio for evaluating blood circulation in a predetermined blood vessel or a predetermined tissue segment according to the current invention. In a step S10 of acquiring angiographic image data, perfusion-related equipment is required to perform the injection of a predetermined contrast agent into the subject S. In further detail, the imaging data is not limited to a single view and is optionally obtained from two views. For example, a predetermined contrast agent is injected in bolus into the left ventricular cavity in a coronary study prior to scanning. The detail of a perfusion technique is not going to be described in details here, but well-known perfusion techniques are generally applicable to the current invention.

In step S20, the blood circulation determination process in one embodiment of the current invention initially generates time density data such as time-density curves (TDCs) at predetermined locations along a selected blood vessel from the angiographic image data. The predetermined locations generally include at least a proximal location and a distal location. The proximal location is proximal to a suspected stenosis location in the selected blood vessel and is substantially free from any blockage for blood circulation. On the other hand, the distal location is distal to the suspected stenosis location in the selected blood vessel and is potentially affected by the blockage for blood circulation.

In step S30, one embodiment of the blood circulation determination process further includes steps or actions that are performed by a combination of various software and hardware components. According to one aspect of the current invention, the blood circulation determination process advantageously determines a predetermined time-based fractional flow reserve (FFR) based upon the angiographic image data that is previously acquired.

Ultimately, the blood circulation determination process determines a predeteimined time-based index ratio such as time-based FFR for evaluating a level of blood circulation between at least two locations such as the proximal location and the distal location in a selected blood vessel in the region of interest in a step S40. In the evaluation, a certain treatment is considered based upon the time-based index ratio. For example, a FFR threshold value of 0.75 is often used among clinicians although some doctors prefer a FFR threshold value of 0.8. In this regard, a range of FFR threshold value from 0.75 to 0.8 is considered to be a concerned range where a patient may require medical treatment. The treatment to a patient in the concerned FFR range depends on a totality of a particular patient's conditions. In general, if a FFR value is larger than the clinically accepted FFR threshold value, no serious treatment is generally needed and a patient can go home with some medication. On the other hand, if a FFR value is smaller than the clinically accepted FFR threshold value, a patient generally needs serious medical attention and requires some serious coronary procedure such as surgery.

It is to be understood, however, that even though numerous characteristics and advantages of the present invention have been set forth in the foregoing description, together with details of the structure and function of the invention, the disclosure is illustrative only, and that although changes may be made in detail, especially in matters of shape, size and arrangement of parts, as well as implementation in software, hardware, or a combination of both, the changes are within the principles of the invention to the full extent indicated by the broad general meaning of the terms in which the appended claims are expressed. 

What is claimed is:
 1. A system for evaluating blood circulation in a blood vessel, comprising; an image data acquiring unit for acquiring imaging data indicating blood circulation in a region of interest (ROI) including at least in a predetermined risk blood vessel; a user interface unit for at least specifying the ROI; an image processing unit connected to said image data acquiring unit for performing ECG gating, motion compensation and background subtraction on the imaging data; a time density generating unit connected to said image processing unit for generating time density data in the ROI from the imaging data at a proximal location and a distal location at least with respect to the predetermined risk blood vessel, wherein the proximal location is proximal to a suspected stenosis in the predetermined risk blood vessel while the distal location is distal to the suspected stenosis; and a time-based index determining unit connected to said time density generating unit for determining based upon the time density data a time-based index for evaluating a level of the blood circulation between the proximal location and the distal location in the ROI.
 2. The system for evaluating blood circulation in a blood vessel according to claim 1 wherein the imaging data includes contrast image data after a contrast agent is injected using a predetermined bolus technique, wherein the imaging data is acquired using said image data acquiring unit of a predetermined modality including X-ray diagnostic apparatuses, ultrasound diagnostic apparatuses, computed tomography (CT) apparatuses, magnetic resonance imaging (MRI) apparatuses, angiography apparatuses and positron emission tomography (PET) apparatuses.
 3. A method of evaluating blood circulation in a blood vessel, comprising; acquiring imaging data indicating blood circulation in a region of interest including at least in a predetermined risk blood vessel; determining time density data from the imaging data at a proximal location and a distal location with respect to the predetermined risk blood vessel, wherein the proximal location is proximal to a suspected stenosis in the predetermined risk blood vessel while the distal location is distal to the suspected stenosis; and determining based upon the time density data a time-based index for evaluating a level of the blood circulation between the proximal location and the distal location in the predetermined risk blood vessel in the region of interest.
 4. The method of evaluating blood circulation in a blood vessel according to claim 3 wherein the time density data includes time density curves indicating density of a predetermined agent over a course of time at each of the proximal location and the distal location.
 5. The method of evaluating blood circulation in a blood vessel according to claim 4 wherein the time-based index is a time-based fractional flow reserve (time-based FFR) as defined by a ratio of time between corresponding points in the time density curves at the proximal location and the distal location.
 6. The method of evaluating blood circulation in a blood vessel according to claim 5 wherein the time-based FFR indicates a level of blockage in blood circulation in the predetermined risk blood vessel between the proximal location and the distal location.
 7. The method of evaluating blood circulation in a blood vessel according to claim 6 wherein the proximal location is inside the predetermined risk blood vessel.
 8. The method of evaluating blood circulation in a blood vessel according to claim 6 wherein the proximal location is inside the predetermined risk blood vessel and proximal to a branching point.
 9. The method of evaluating blood circulation in a blood vessel according to claim 6 wherein the proximal location is inside a predetermined healthy blood vessel substantially free from stenosis.
 10. The method of evaluating blood circulation in a blood vessel according to claim 6 wherein the distal location is inside the predetermined risk blood vessel distal to a blockage.
 11. The method of evaluating blood circulation in a blood vessel according to claim 6 wherein the distal location is in a predetermined area inside the predetermined risk blood vessel and the predetermined area is distal to the proximal location.
 12. The method of evaluating blood circulation in a blood vessel according to claim 6 wherein the distal location is over a predetermined line inside the predetermined risk blood vessel distal to the proximal location.
 13. The method of evaluating blood circulation in a blood vessel according to claim 6 wherein the distal location is a tissue area outside the predetermined risk blood vessel but distal to the proximal location.
 14. The method of evaluating blood circulation in a blood vessel according to claim 5 wherein the corresponding points in time include one of time-to-peak, mean-transit-time and upward slope in the time density curves.
 15. The method of evaluating blood circulation in a blood vessel according to claim 3 where the imaging data includes a reference blood vessel and is acquired from two views.
 16. A method of evaluating blood circulation in a blood vessel, comprising; acquiring imaging data indicating blood circulation in a region of interest including a predetermined risk blood vessel and a predetermined reference blood vessel that is substantially from stenosis, comparable in size and located near the predetermined risk blood vessel; determining time density data of the predetermined risk blood vessel and the predetermined reference blood vessel from the imaging data in the region of interest; and determining based upon the time density data a time-based index for evaluating a level of the blood circulation in the predetermined risk blood vessel with respect to the predetermined reference blood vessel in the region of interest.
 17. The method of evaluating blood circulation in a blood vessel according to claim 16 wherein the imaging data includes contrast image data after a contrast agent is injected using a predetermined bolus technique.
 18. The method of evaluating blood circulation in a blood vessel according to claim 16 wherein the imaging data is acquired using a predetermined modality including X-ray diagnostic apparatuses, ultrasound diagnostic apparatuses, computed tomography (CT) apparatuses, magnetic resonance imaging (MRI) apparatuses, angiography apparatuses and positron emission tomography (PET) apparatuses.
 19. The method of evaluating blood circulation in a blood vessel according to claim 16 wherein the time density data includes time density curves indicating density of a predetermined agent over a course of time in the predetermined risk blood vessel and the predetermined reference blood vessel.
 20. The method of evaluating blood circulation in a blood vessel according to claim 19 wherein a pair of the time density curves is generated for each of the predetermined risk blood vessel and the predetermined reference blood vessel and the two density curves respectively correspond the time density data at a proximal location and a distal location along each of the predetermined risk blood vessel and the predetermined reference blood vessel.
 21. The method of evaluating blood circulation in a blood vessel according to claim 20 wherein the time-based index is a time-based fractional flow reserve (time-based FFR) as defined by a first ratio of time between corresponding points in the time density curves for the predetermined risk blood vessel and a second ratio of time between the corresponding points in the time density curves for the predetermined reference blood vessel.
 22. The method of evaluating blood circulation in a blood vessel according to claim 21 wherein the corresponding points in time include one of time-to-peak and mean-transit-time in the time density curves.
 23. The method of evaluating blood circulation in a blood vessel according to claim 19 wherein the predetermined risk blood vessel and the predetermined reference blood vessel branching from a common blood vessel, a pair of the time density curves being generated for both of the predetermined risk blood vessel and the predetermined reference blood vessel and the two density curves respectively correspond the time density data at a distal location that is distal to a suspected stenosis in the predetermined risk blood vessel and a comparable distal location in the predetermined reference blood vessel.
 24. The method of evaluating blood circulation in a blood vessel according to claim 23 wherein the time-based index is a time-based fractional flow reserve (time-based FFR) as defined by a ratio of time between corresponding points in the time density curves for the predetermined risk blood vessel and the predetermined reference blood vessel.
 25. The method of evaluating blood circulation in a blood vessel according to claim 24 wherein the corresponding points in time include one of time-to-peak, mean-transit-time and upward slope in the time density curves.
 26. The method of evaluating blood circulation in a blood vessel according to claim 16 where the imaging data for the predetermined reference blood vessel is acquired from two views.
 27. The method of evaluating blood circulation in a blood vessel according to claim 16 where a ratio of a blood volume parameter at a distal location and a proximal location in the predetermined reference blood vessel is approximated by the time density data. 